Bones are a common tissue calcified in our bodies and serve to support our bodies through a reforming procedure. The causes of bone diseases may be mainly divided into three: first, an abnormal size in the growth procedure; second, an imbalance between bone formation by osteoblasts and bone absorption by osteoclasts in the bone remodeling procedure; and third, abnormality in bone calcification or mineralization.
The transforming growth factor-beta (TGF-β) superfamily is composed of 40 or more members, such as Nodal, Activin, and bone morphogenetic proteins (BMPs). As for TGF-β signaling, particular types I and II serine/threonine kinase receptors form complexes, which penetrate plasma membranes through a form of a heteromeric complex to first transmit signals. TGF-β/BMPs are known to be involved in various functions in the body and bone formation of the mammalian development procedure. The disturbance of TGF-β/BMP signaling affects multiple bone-related diseases, such as tumor metastasis, phocomelia, and arthritis.
The bones of the body are a very dynamic organ such that the bones are gradually degraded every day, and the filling with new bones occurs by the amount of degraded bones, and thus, homeostasis is maintained. When the activity of one type cells between osteoclasts for degrading bones and osteoblasts for regenerating bones is increased or decreased, several diseases may be caused due to the destruction of homeostasis. The increase in activity of osteoclasts that absorb bones causes diseases, such as osteoporosis, in which the degradation of bones is promoted and the bones are thin and easily broken, and the increase in activity of the osteoblasts causes bone deformities or bone calcification due to increased bone density. Therefore, the balance between osteoclasts and osteoblasts is important.
As for drugs known until now, Korean Bone Bank, which is the Biosimilar pharmaceutical company, recently received approval for clinical test of “Rafugen” as a bone morphogenetic protein from Korean Food & Drug Administration and enter the clinical test thereof. Additionally, Daewoong released “Novosis” as a novel concept bio-fusion medical machine in which bone morphogenetic protein, “BMP2”, is grafted on the artificial bones. The Novosis will be variously utilized in the bone graft-related treatment including implantation, in which the bones adhere better and the operation time and bleeding time decrease compared with auto-transplantation, and thus fast recovery is expected. Additionally, Dong-Wha Pharm released “DW1350”, as a drug having excellent functions of inhibiting osteoclasts and promoting osteoblasts, but such a drug has been continuously subjected to clinical tests until now and is not released in Korea.
Throughout the entire specification, many papers and patent documents are referenced and their citations are represented. The disclosure of the cited papers and patent documents are entirely incorporated by reference into the present specification, and the level of the technical field within which the present invention falls and the details of the present invention are explained more clearly.